In previous studies, we have devised techniques for preparing viable, dispersed bovine and human parathyroid cells. Such cell preparations offer several advantages, including ease of handling uniform exposure to incubation medium, and the feasibility of quantitating directly intracellular mediators of hormone action such as cyclic AMP (cAMP). In studies to date with dispersed bovine cells, we have shown a close correlation between intracellular cAMP and parathyroid hormone (PTH) secretion. In other systems cAMP levels are regulated by adenylate cyclase and phosphodiesterase(s), while the effects of cAMP appear to be mediated by cAMP-dependent protein kinases. IN dispersed bovine parathyroid cells, we propose to study (1) the mechanism by which calcium and other secretagogues regulate adenylate cyclase and phosphodiesterase activities. (2) The potential mediatory role of cAMP will be studied directly in terms of cAMP effects on protein kinase. Our previous studies with dispersed human parathyroid cells have suggested abnormal control of secretion by calcium in primary hyperparathyroidism. Employing normal human parathyroid cells as control, we propose to investigate (1) the control of secretion in a larger group of patients with hyperparathyroidism to determine if specific functional derangements are associated with particular histologic and hereditary forms of the disorder. (2) The effect of calcium on adenylate cyclase and phosphodiesterase activities will be assessed to investigate possible biochemical bases for the abnormal secretory control. (3) Potential abnormalities in the control of cell proliferation by calcium will be assessed by tritiated thymidine incorporation into DNA. (4) Parathyroid suppressibility by calcium in vivo and vitro in primary hyperparathyroidism will be compared to document further the validity of dispersed cells to study parathyroid function in man. This series of studies is designed to define better the molecular basis of the control of PTH secretion in abnormal and normal parathyroid tissue. In this manner, it may be possible to understand, in part, the pathophysiology of primary hyperparathyroidism.